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Clinical experience on 3.0 T systems in Niigata, 1996 to 2002.

High-field human magnetic resonance imaging (MRI) systems developed over the recent years have contributed significantly to the field of functional MRI and multinuclear spectroscopy. As more experience is gained, it has become apparent that high-field systems, especially those at 3.0 T, possess significant advantages in the clinical setting over conventional MRI systems. High-field MRI is promising as an all-in-one system for both structural and functional assessments. This review summarizes the exciting features of clinical imaging based on our cumulative 6-year experience on various 3.0 T systems.

Brain Mapping↗

Two types of ipsilateral reorganization in congenital hemiparesis: a TMS and fMRI study.

Reorganization after early brain injuries is not only determined by the maturational stage of the CNS at the time of the insult (timing), but also by the structural properties, location and extent of the lesion. This study addresses the impact of different lesion extents on the type of reorganization induced in a cohort of patients with lesions of uniform structure and location (unilateral periventricular defects) and similar timing (early third trimester of pregnancy). Twelve young adult patients with congenital hemiparesis and 10 age-matched controls were studied. The severity of structural damage to hand motor projections of the cortico-spinal tract was assessed on semi-coronal MRI reconstructions along anatomical landmarks of cortico-spinal tract somatotopy. The functional integrity of these crossed cortico-spinal projections in the affected hemisphere, as well as the presence of any abnormal ipsilateral projections to the paretic hand, was examined by transcranial magnetic stimulation (TMS). Cortical activation during simple voluntary hand movements was studied by functional MRI (fMRI). Patients with small lesions (SL; n = 4) and only mild hand motor impairment possessed intact crossed cortico-spinal projections to the paretic hand, whereas no motor response could be elicited by TMS of the affected hemisphere in those with large lesions (LL; n = 6) and more severe hand motor impairment. Evidence for compensatory recruitment of the unaffected hemisphere was found in both subgroups. In the SL group, fMRI demonstrated ipsilateral activation of premotor areas, without any abnormal projections to the paretic hand originating from these sites. In the LL group, such abnormal ipsilateral projections to the paretic hand were indeed found, and fMRI confirmed cortical activation of an abnormal ipsilateral hand motor representation in the primary sensorimotor region of the unaffected hemisphere. Two patients with intermediate-sized lesions presented combined features of both groups (SL, LL). In conclusion, this study provides evidence that the type of cortico-spinal reorganization depends on the extent of the brain lesion. We propose that involvement of the ipsilateral hemisphere can be (i) of the premotor type, i.e. without ipsilateral motor projections but with significant activation of ipsilateral premotor areas, or (ii) of the primary motor type, i.e. with abnormal ipsilateral cortico-spinal projections to the paretic hand.

Adolescent↗

Prefrontal and striatal activation in elderly subjects during concurrent implicit and explicit sequence learning.

Decreased function in the prefrontal cortex (PFC) is regarded as a primary mechanism of cognitive aging. However, despite a strong association between the prefrontal cortex and the neostriatum, the role of the neostriatum in cognitive aging is less certain. In the current study, event-related functional MRI was used to distinguish the cognitive contributions of neostriatal and prefrontal function in elderly versus young subjects. Twenty healthy subjects, 9 elderly (mean age 67.6 years), and 11 young (mean age 22 years) performed a concurrent implicit and explicit sequence learning task while undergoing functional MR imaging. Both groups showed learning in both the implicit and explicit task conditions. Relative to the young subjects, the elderly subjects showed decreased activation in the left PFC during both implicit and explicit learning, decreased activation in the right putamen during implicit learning, and increased activation in the right PFC during explicit learning. Our results support the theory that changes in a network of brain regions, including the dorsolateral prefrontal cortex and the striatum, are related to cognitive aging. Moreover, these changes are observed during an implicit task, and thus do not seem to be mediated by awareness.

Adult↗

Trauma modulates amygdala and medial prefrontal responses to consciously attended fear.

Effective fear processing relies on the amygdala and medial prefrontal cortex (MPFC). Post-trauma reactions provide a compelling model for examining how the heightened experience of fear impacts these systems. Post-traumatic stress disorder (PTSD) has been associated with excessive amygdala and a lack of MPFC activity in response to nonconscious facial signals of fear, but responses to consciously processed facial fear stimuli have not been examined. We used functional MRI to elucidate the effect of trauma reactions on amygdala-MPFC function during an overt fear perception task. Subjects with PTSD (n = 13) and matched non-traumatized healthy subjects (n = 13) viewed 15 blocks of eight fearful face stimuli alternating pseudorandomly with 15 blocks of neutral faces (stimulus duration 500 ms; ISI 767 ms). We used random effects analyses in SPM2 to examine within- and between-group differences in the MPFC and amygdala search regions of interest. Time series data were used to examine amygdala-MPFC associations and changes across the first (Early) versus second (Late) phases of the experiment. Relative to non-traumatized subjects, PTSD subjects showed a marked bilateral reduction in MPFC activity (in particular, right anterior cingulate cortex, ACC), which showed a different Early-Late pattern to non-traumatized subjects and was more pronounced with greater trauma impact and symptomatology. PTSD subjects also showed a small but significant enhancement in left amygdala activity, most apparent during the Late phase, but reduction in Early right amygdala response. Over the time course, trauma was related to a distinct pattern of ACC and amygdala connections. The findings suggest that major life trauma may disrupt the normal pattern of medial prefrontal and amygdala regulation.

Adult↗

CPD - education and self-assessment: functional imaging in epilepsy.

Functional imaging plays a growing role in the clinical assessment and research investigation of patients with epilepsy. This article reviews the literature on functional MRI (fMRI) investigation of EEG activity, fMRI evaluation of cognitive and motor functions, magnetic resonance spectroscopy (MRS), single photon emission computed tomography (SPECT) and positron emission tomography (PET) in epilepsy. The place of these techniques in clinical evaluation and their contribution to a better neurobiological understanding of epilepsy are discussed.

Brain↗

BOLD magnetic resonance imaging of skeletal muscle.

Blood-oxygen-level-dependent (BOLD) imaging was a concept introduced in 1990 for evaluating brain activation. The method relies on magnetic resonance imaging (MRI) contrast resulting from changes in the microvascular ratio of oxyhaemoglobin (oxyHb) to deoxyhaemoglobin (deoxyHb). OxyHb is diamagnetic, whereas deoxyHb is paramagnetic, which produces a local bulk magnetic susceptibility effect and subsequent MRI signal change. The changes are typically observed in T(2)*-weighted functional MRI scans. However, there has recently been interest in BOLD as a way to evaluate microcirculation of any normal or diseased tissue. This review focuses on the application of BOLD imaging in the understanding of normal and diseased skeletal muscle. In addition we present new findings showing the possible application of BOLD imaging with hyperoxia for evaluating skeletal muscle physiology.

Humans↗

Frontal lobes and human memory: insights from functional neuroimaging.

The new functional neuroimaging techniques, PET and functional MRI (fMRI), offer sufficient experimental flexibility and spatial resolution to explore the functional neuroanatomical bases of different memory stages and processes. They have had a particular impact on our understanding of the role of the frontal cortex in memory processing. We review the insights that have been gained, and attempt a synthesis of the findings from functional imaging studies of working memory, encoding in episodic memory and retrieval from episodic memory. Though these different aspects of memory have usually been studied in isolation, we suggest that there is sufficient convergence with respect to frontal activations to make such a synthesis worthwhile. We concentrate in particular on three regions of the lateral frontal cortex--ventrolateral, dorsolateral and anterior--that are consistently activated in these studies, and attribute these activations to the updating/maintenance of information, the selection/manipulation/monitoring of that information, and the selection of processes/subgoals, respectively. We also acknowledge a number of empirical inconsistencies associated with this synthesis, and suggest possible reasons for these. More generally, we predict that the resolution of questions concerning the functional neuroanatomical subdivisions of the frontal cortex will ultimately depend on a fuller cognitive psychological fractionation of memory control processes, an enterprise that will be guided and tested by experimentation. We expect that the neuroimaging techniques will provide an important part of this enterprise.

Animals↗

Cholinergic challenge in Alzheimer patients and mild cognitive impairment differentially affects hippocampal activation--a pharmacological fMRI study.

Pharmacological functional MRI (phMRI) examines the impact of pharmacologically induced neurochemical changes on brain function at a system level. The current phMRI study directly compared effects of cholinergic stimulation on brain function between patients with Alzheimer's disease and mild cognitive impairment, a disease stage preceding the development of Alzheimer's disease. Brain function during recognition of (un)familiar information was examined for changes after exposure to galantamine, a cholinesterase inhibitor used for treating memory deficits in Alzheimer's disease. Alzheimer patients [n = 18; age 74.5 years +/- 8.2; Mini-Mental State Examination (MMSE) 22.5 +/- 2.4] and patients with mild cognitive impairment (n = 28; mean age 73.6 +/- 7.5; MMSE 27.0 +/- 1.2) were scanned during face recognition under three different conditions: at baseline, and after acute (single dose) and prolonged exposure (5 days) to galantamine. Functional data were analysed in an event-related fashion. In both groups, acute exposure produced strong increases in brain activation (Z > 3.1). Prolonged exposure produced less strong effects that mainly involved decreases in activation (Z > 3.1). In mild cognitive impairment, acute exposure increased activation in posterior cingulate, left inferior parietal, and anterior temporal lobe. Prolonged exposure decreased activation in similar posterior cingulate areas, and in bilateral prefrontal areas. Effects were stronger for positive ('familiar') than for negative ('unfamiliar') decisions, indicating that the effect was specific to memory retrieval. In Alzheimer patients, acute exposure increased activation bilaterally in hippocampal areas, whereas prolonged exposure decreased activation in these areas. Effects were more pronounced for negative than for positive decisions, suggesting a preferential effect on memory encoding. Unique profiles of signal reactivity were found in a number of areas, including left inferior parietal lobe and left hippocampus proper. The reactivity of posterior cingulate and hippocampal structures to cholinergic challenge suggests a key role of the cholinergic system in the functional processes that lead to Alzheimer's disease. The differential response to cholinergic challenge in mild cognitive impairment and Alzheimer patients may reflect a difference in the functional status of the cholinergic system between both groups, which is in line with recent results showing a differential clinical response to cholinergic treatment.

Aged↗

Motor system activation after subcortical stroke depends on corticospinal system integrity.

Movement-related brain activation patterns after subcortical stroke are characterized by relative overactivations in cortical motor areas compared with controls. In patients able to perform a motor task, overactivations are greater in those with more motor impairment. We hypothesized that recruitment of motor regions would shift from primary to secondary motor networks in response to impaired functional integrity of the corticospinal system (CSS). We measured the magnitude of brain activation using functional MRI during a motor task in eight chronic subcortical stroke patients. CSS functional integrity was assessed using transcranial magnetic stimulation to obtain stimulus/response curves for the affected first dorsal interosseus muscle, with a shallower gradient representing increasing disruption of CSS functional integrity. A negative correlation between the gradient of stimulus/response curve and magnitude of task-related brain activation was found in several motor-related regions, including ipsilesional posterior primary motor cortex [Brodmann area (BA) 4p], contralesional anterior primary motor cortex (BA 4a), bilateral premotor cortex, supplementary motor area, intraparietal sulcus, dorsolateral prefrontal cortex and contralesional superior cingulate sulcus. There were no significant positive correlations in any brain region. These results suggest that impaired functional integrity of the CSS is associated with recruitment of secondary motor networks in both hemispheres in an attempt to generate motor output to spinal cord motoneurons. Secondary motor regions are less efficient at generating motor output so this reorganization can only be considered partially successful in reducing motor impairment after stroke.

Adult↗

[Autism: neuroimaging].

Autism is a neurodevelopmental disorder with a range of clinical presentations. These presentations vary from mild to severe and are referred to as autism spectrum disorders. The most common clinical sign of autism spectrum disorders is social interaction impairment, which is associated with verbal and non-verbal communication deficits and stereotyped and repetitive behaviors. Thanks to recent brain imaging studies, scientists are getting a better idea of the neural circuits involved in autism spectrum disorders. Indeed, functional brain imaging, such as positron emission tomography, single foton emission tomography and functional MRI have opened a new perspective to study normal and pathological brain functioning. Three independent studies have found anatomical and rest functional temporal lobe abnormalities in autistic patients. These alterations are localized in the superior temporal sulcus bilaterally, an area which is critical for perception of key social stimuli. In addition, functional studies have shown hypoactivation of most areas implicated in social perception (face and voice perception) and social cognition (theory of mind). These data suggest an abnormal functioning of the social brain network in autism. The understanding of the functional alterations of this important mechanism may drive the elaboration of new and more adequate social re-educative strategies for autistic patients.

Auditory Perception↗

Functional imaging in epilepsy.

Functional imaging plays a growing role in the clinical assessment and research investigation of patients with epilepsy. This article reviews the literature on functional MRI (fMRI) investigation of EEG activity, fMRI evaluation of cognitive and motor functions, magnetic resonance spectroscopy (MRS), single photon emission computed tomography (SPECT) and positron emission tomography (PET) in epilepsy. The place of these techniques in clinical evaluation and their contribution to a better neurobiological understanding of epilepsy are discussed.

Anticonvulsants↗

[Diagnosis of epilepsy].

0.5-1% of the population suffers from epilepsy, while another 5% undergoes diagnostic evaluations due to the possibility of epilepsy. In the case of suspected epileptic seizures we face the following questions: Is it an epileptic seizure? The main and most frequent differential-diagnostic problems are the psychogenic non-epileptic seizures ("pseudo-seizures") and the convulsive syncope, which is often caused by heart disorders. Is it epilepsy? After an unprovoked seizure, the information on recurrence risk is an important question. The reoccurrence is more possible if a known etiological factor is present or the EEG shows epileptiform discharges. After an isolated epileptic seizure, the EEG is specific to epilepsy in 30-50% of cases. The EEG should take place within 24 hours postictally. If the EEG shows no epileptiform potentials, a sleep-EEG is required. What is the cause of seizures? Hippocampal sclerosis, benign tumors, and malformations of the cortical development are the most frequent causes of the focal epilepsy. Three potentially life-threatening conditions may cause chronic epilepsy: vascular malformations, tumors, and neuroinfections. The diagnosis in theses cases can usually be achieved by MRI, therefore, MRI is obligatory in all epilepsies starting in adulthood. The presence of epileptogenic lesion has a prognostic significance in treatment. If the MRI shows a circumscribed lesion then the pharmacological treatment will likely to be unsuccessful, while surgery may result in seizure freedom. The new and quantitative MRI techniques, such as volumetry, T2-relaxometry, MR-spectroscopy, and functional MRI play a growing role in the epilepsy diagnosis.

Brain Neoplasms↗

[Neurofunctional tests in presurgical strategies for partial epilepsies].

The presurgical evaluation of drug-resistant partial epilepsies primarily relies on two major investigations, including a long term video-EEG monitoring which aimed at recording the patient's typical seizures, and a specifically designed high quality magnetic resonance imaging (MRI). The latter demonstrates an abnormality within the epileptogenic lobe in the majority of cases, which might not, however, necessarily match the epileptogenic zone. Numerous functional neuro-imaging techniques have been progressively added to the pre-surgical evaluation of refractory partial epilepsies, such as the study of cerebral glucose metabolism, benzodiazepine receptor availability, and methionine incorporation using positron emission tomography (PET), the evaluation of ictal cerebral blood flow changes using single photon emission computerized tomography (SPECT), the measurement of N-acetyl-aspartate concentration with magnetic resonance spectroscopy, and the mapping of eloquent areas using functional MRI. These investigations can help to confirm the origin of seizure onset previously suggested by MRI and electro-clinical data, and provide independent prognostic information regarding the chance of a successful surgical treatment. Moreover, functional neuro-imaging data can have a critical diagnostic value when MRI is strictly normal or shows multifocal abnormalities. However, the variety and rapid evolution of functional neuro-imaging techniques makes it difficult to propose a standard protocol. Finally, it remains mandatory to proceed to an intracranial EEG investigation in a substantial number of patients, including the majority of those suffering from an extra-temporal epilepsy.

Electroencephalography↗

MRI of the hypopharynx with provocative maneuvers.

The purpose of this study was to assess the validity of magnetic resonance (MR) functional images of the hypopharynx. Following T2-weighted spin-echo sequences during quiet respiration, contrast enhanced 2D-Turbo-FLASH sequences were obtained during Valsalva-maneuver, quiet respiration, A- and U-phonation, respectively. Tumor detection was clearly improved using functional MRI (sensitivity of 97.4%, specificity 83.3%, accuracy 95.5%) when compared with MRI during quiet respiration (sensitivity of 87.1%, specificity 33.3%, accuracy 80%). Rapid MR sequences such as 2D-Turbo FLASH allow functional imaging of the hypopharynx, thereby improving MR diagnosis of hypopharyngeal tumors.

Adult↗

Theoretical noise model for oxygenation-sensitive magnetic resonance imaging.

Contrast-to-noise ratio (CNR) in blood oxygenation level-dependent (BOLD) based functional MRI (fMRI) studies is a fundamental parameter to determine statistical significance and therefore to map functional activation in the brain. The CNR is defined here as BOLD contrast with respect to temporal fluctuation. In this study, a theoretical noise model based on oxygenation-sensitive MRI signal formation is proposed. No matter what the noise sources may be in the signal acquired by a gradient-echo echo-planar imaging pulse sequence, there are only three noise elements: apparent spin density fluctuations, S(0)(t); transverse relaxation rate fluctuations, R(2) (*)(t); and thermal noise, n(t). The noise contributions from S(0)(t), R(2) (*)(t), and n(t) to voxel time course fluctuations were evaluated as a function of echo time (TE) at 3 T. Both noise contributions caused by S(0)(t) and R(2) (*)(t) are significantly larger than that of thermal noise when TE = 30 ms. In addition, the fluctuations between S(0)(t) and R(2) (*)(t) are cross-correlated and become a noise factor that is large enough and cannot be ignored. The experimentally measured TE dependences of noise, temporal signal-to-noise ratio, and BOLD CNR in finger-tapping activation regions were consistent with the proposed model. Furthermore, the proposed theoretical models not only unified previously proposed BOLD CNR models, but also provided mechanisms for interpreting apparent controversies and limitations that exist in the literature.

Adolescent↗

Functional neuroanatomy of visuo-spatial working memory in Turner syndrome.

Turner syndrome (TS), a genetic disorder characterized by the absence of an X chromosome in females, has been associated with cognitive and visuo-spatial processing impairments. We utilized functional MRI (fMRI) to investigate the neural substrates that underlie observed deficits in executive functioning and visuo-spatial processing. Eleven females with TS and 14 typically developing females (ages 7-20) underwent fMRI scanning while performing 1-back and 2-back versions of a standard visuo-spatial working memory (WM) task. On both tasks, TS subjects performed worse than control subjects. Compared with controls, TS subjects showed increased activation in the left and right supramarginal gyrus (SMG) during the 1-back task and decreased activation in these regions during the 2-back task. In addition, decreased activation in the left and right dorsolateral prefrontal cortex (DLPFC) and caudate nucleus was observed during the 2-back task in TS subjects. Activation differences localized to the SMG, in the inferior parietal lobe, may reflect deficits in visuo-spatial encoding and WM storage mechanisms in TS. In addition, deficits in the DLPFC and caudate may be related to deficits in executive function during WM performance. Together these findings point to deficits in frontal-striatal and frontal-parietal circuits subserving multiple WM functions in TS.

Adolescent↗

Correlations in low-frequency BOLD fluctuations reflect cortico-cortical connections.

Cross-correlation of low-frequency temporal fluctuations (<0.08 Hz) was used to correlate widely separated anatomic regions during continuous performance of a spatial working memory task. The regions of highest correlation to right-hemisphere dorsolateral prefrontal cortex correspond to the regions of largest baseline signal change in a conventional block-style functional MRI paradigm. Additionally, it is shown that the correlations between elements of the functional network increase during performance of a task that activates the network when compared to a task that does not directly stimulate the functionally connected network.

Attention↗

[Morphological and functional pelvic floor disorders from the gynecological viewpoint].

PURPOSE: The following article is designed to describe the diagnostics and therapy of morphological and functional defects in the female pelvic floor from a gynaecological point of view. Assessment of the relevance of imaging techniques is of particular importance. MATERIAL AND METHODS: The main diagnoses are: in the anterior compartment of the pelvic floor, urethro- cystocele; in the middle compartment, uterine descent/prolapse or enterocele; and in the posterior compartment, rectocele. They are clinically examined by means of a standardised gynaecological examination and classified according to recommendations from the International Continence Society (ICS) in order to obtain internationally comparable results. Comparison with the usual imaging procedures (introitus- and perineal sonography, colpocystorectography/defaecography and functional MRI of the pelvic floor) are described and critically discussed. The most important functions affected are storage and evacuation of the bladder and rectum. They are clinically examined by means of stress test and padweigh test and technically examined using urodynamics, sphincter-rectum manometry and EMG. Imaging procedures play a very important role here also. RESULTS: Comparison of clinical and imaging procedures shows that the two methods are at present limited in comparability, mainly because different points of reference are used to quantify results. The line of the hymen is a good point of reference in grading descent and prolapse. During the gynaecological examination, the three compartments can readily be assessed separately by use of split gynaecological specula. This is presently practically impossible using imaging procedures. The pubococcygeal line is generally used to describe findings. DISCUSSION: Scientific progress can only be expected if and when these problems are studied as a whole. Imaging procedures have securely established themselves in the diagnostic repertoire, but do not as yet influence therapy decisions. The indication and choice of operation depend on the severity of the patient's symptoms the clinical findings and the results of urodynamic investigations. Dynamic CTG is presently the most reliable method of showing all three compartments at rest and during function. It has largely replaced colpocystorectography. Sonography is found to be varied in ist results at the moment.

Female↗